3,3,6-tribromo-2-oxo-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester | 1090903-68-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 3,3,6-tribromo-2-oxo-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester
• 英文别名: methyl 3,3,6-tribromo-2-oxo-1H-indole-4-carboxylate
• CAS: 1090903-68-6
• 化学式: C₁₀H₆Br₃NO₃
• 分子量: 427.875
• InChiKey: KZLOSOTYUOSOCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,3,6-tribromo-2-oxo-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester 在 锌 乙酸乙酯 、 水 、 Brine 作用下， 以 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 0.58h， 生成 6-溴-2-氧代-2,3-二氢-1h-吲哚-4-羧酸甲酯
  参考文献：
  名称：

  Benzimidazolone Chymase Inhibitors

  摘要：

  公开了一种小分子抑制剂，其在治疗涉及chymase的各种疾病和病况方面是有用的。

  公开号：

  US20100240702A1
• 作为产物：
  描述：

  6-溴-4-吲哚甲酸甲酯 在 pyridinium hydrobromide perbromide 、 叔丁醇 作用下， 反应 2.0h， 以88%的产率得到3,3,6-tribromo-2-oxo-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategies

  摘要：

  Chymase plays an important and diverse role in the homeostasis of a number of cardiovascular processes. Herein, we describe the identification of potent, selective chymase inhibitors, developed using fragment-based, structure-guided linking and optimization techniques. High-concentration biophysical screening methods followed by high-throughput crystallography identified an oxindole fragment bound to the S1 pocket of the protein exhibiting a novel interaction pattern hitherto not observed in chymase inhibitors. X-ray crystallographic structures were used to guide the elaboration/linking of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over cathepsin G and that mitigated a number of liabilities associated with poor physicochemical properties of the series it was derived from.

  DOI：

  10.1021/jm400138z
• 作为试剂：
  描述：

  3-[3-(5-Chloro-2-oxo-2,3-dihydro-benzooxazol-7-ylmethyl)-2-oxo-2,3-dihydro-benzoimidazol-1-yl]-hexanoic acid methyl ester 、 氢氧化锂 、 盐酸 在 3,3,6-tribromo-2-oxo-2,3-dihydro-1H-indole-4-carboxylic acid methyl ester 、 crude material 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以to give the title compound 20 mg (0.04 mmol, 54%)的产率得到3-[3-(5-Chloro-2-oxo-2,3-dihydro-benzooxazol-7-ylmethyl)-2-oxo-2,3-dihydro-benzoimidazol-1-yl]-hexanoic acid
  参考文献：
  名称：

  Benzimidazolone chymase inhibitors

  摘要：

  本发明揭示了一种小分子抑制剂，可用于治疗涉及痰蛋白酶的各种疾病和病况。

  公开号：

  US09150556B2

文献信息

• Benzimidazolone Chymase Inhibitors
  申请人：Abeywardane Asitha

  公开号：US20100240702A1

  公开（公告）日：2010-09-23

  Disclosed are small molecule inhibitors which are useful in treating various diseases and conditions involving chymase.

  公开了一种小分子抑制剂，其在治疗涉及chymase的各种疾病和病况方面是有用的。
• BENZIMIDAZOLONE CHYMASE INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2152674B1

  公开（公告）日：2011-08-03
• US9150556B2
  申请人：——

  公开号：US9150556B2

  公开（公告）日：2015-10-06
• [EN] BENZIMIDAZOLONE CHYMASE INHIBITORS<br/>[FR] INHIBITEURS DE BENZIMIDAZOLONE CHYMASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2008147697A1

  公开（公告）日：2008-12-04

  [EN] Disclosed are small molecule inhibitors which are useful in treating various diseases and conditions involving chymase.
  [FR] L'invention concerne des inhibiteurs à petites molécules qui sont utiles dans le traitement de diverses maladies et affections impliquant la chymase.
• Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategies
  作者：Steven J. Taylor、Anil K. Padyana、Asitha Abeywardane、Shuang Liang、Ming-Hong Hao、Stéphane De Lombaert、John Proudfoot、Bennett S. Farmer、Xiang Li、Brandon Collins、Leslie Martin、Daniel R. Albaugh、Melissa Hill-Drzewi、Steven S. Pullen、Hidenori Takahashi

  DOI：10.1021/jm400138z

  日期：2013.6.13

  Chymase plays an important and diverse role in the homeostasis of a number of cardiovascular processes. Herein, we describe the identification of potent, selective chymase inhibitors, developed using fragment-based, structure-guided linking and optimization techniques. High-concentration biophysical screening methods followed by high-throughput crystallography identified an oxindole fragment bound to the S1 pocket of the protein exhibiting a novel interaction pattern hitherto not observed in chymase inhibitors. X-ray crystallographic structures were used to guide the elaboration/linking of the fragment, ultimately leading to a potent inhibitor that was >100-fold selective over cathepsin G and that mitigated a number of liabilities associated with poor physicochemical properties of the series it was derived from.